The long term goal of this research is to understand the molecular basis of calcium action in cell processes. Specifically, the proposed research deals with studies of calmodulin and calmodulin binding proteins in normal and virus-transformed chicken embryo fibroblasts. The approach in these studies is one combining quantitative cell biology and protein chemistry. The subcellular localization, biosynthesis and biochemical characterization of calmodulin, calmodulin binding proteins and calmodulin regulated enzyme activities in normal and transformed cells are the major investigations around which this research is oriented. Calmodulin is a 148-residue protein that binds four moles of calcium per mole of protein. While calmodulin does not have any detectable enzymatic activity, it will regulate a variety of enzymes in vitro in a calcium dependent manner. The primary structure and effector activities of calmodulin are highly conserved throughout vertebrate, invertebrate and plant species. Calmodulin's ubiquitous distribution among eukaryotes and highly conserved structure and function among plant and animal phyla suggest that it may be playing a fundamental role in cell function. Calmodulin's multiple, in vitro biochemical activities suggest that it may be a pleiotropic regulator in some cells. Historically, pathophysiological and mutant systems have been valuable tools in demonstrating the physiological importance of in vitro biochemical reactions. The chicken embryo fibroblast-virus transformation system was the first system described in which there are alternations in calmodulin metabolism. The availability of a variety of virus mutants that differ in their ability to induce cell transformation and elicit alterations in calmodulin metabolism provide excellent biological tools for the further exploration of this phenomenology. Because of calmodulin's invariant presence and multiple activities, the information obtained and the methods developed in studies of fibroblast calmodulin will be of general biomedical importance. The information gained from these studies will increase our nowledge of how calcium regulates cellular processes, and the direct comparison of normal and pathological states may provide new insights into the molecular and cellular basis of disease states.